Various monoclonal antibodies have been developed over the years in an attempt to find substances which have binding specificity to tumor-associated antigens It has been hoped that these monoclonal antibodies would be useful in the diagnosis and treatment of tumors.
Monoclonal antibodies are produced by cell lines known as hybridomas. Hybridomas can be created using tumor tissue such that the monoclonal antibodies produced therefrom have binding affinity to antigens associated with the tumor tissue. Most monoclonal antibodies are disadvantageous in that they have either (1) an extreme binding specificity, i.e., they are not capable of binding to many tumor types other than those which are very closely related to the tumor from which they were developed or (2) an extreme lack of binding specificity. i.e. they bind to almost all types of cells whether malignant or non-malignant. As a result, these monoclonal antibodies are generally not clinically useful because due to (1) their extreme binding specificity, a unique monoclonal antibody needs to be developed for each tumor to be diagnosed or treated, or (2) their extreme lack of binding specificity, the monoclonal antibody is incapable of differentiating between malignant and non-malignant cells.
In spite of the concerns which have arisen regarding the usefulness of monoclonal antibodies in diagnostic and therapeutic methods, it is still believed that monoclonal antibodies can be developed which are organ specific, i.e., capable of binding to antigens associated with only a particular organ, but which, given their organ-specificity, are capable of binding to an antigen that is associated with many different types of tumors arising in the particular organ.
Prostate carcinoma is one of the most prevalent malignancies among men in the United States. It is postulated that the disease is often present but undetected in the male population. Moreover, it has been noted that prostate carcinoma often exhibits a long latency period. Further prostate carcinoma is known for its high metastatic potential. For these reasons, it has been desired to develop a substance or substances useful for diagnosing, in vivo or in vitro, the presence of prostate tumors and for treating such tumors, especially once the tumors have metastasized.
Various monoclonal antibodies to prostate antigenic markers have been previously described. These previously-described monoclonal antibodies bind to either prostate-specific antigen (PSA) (Wang, M.C. et al, Urol., 17:159-169 (1979)), specifically incorporated herein by reference, or prostatic acid phosphatase (PAP) (Chu, T.M. et al, Urol., 15:319-322 (1978)), specifically incorporated herein by reference, or both. These previously-described monoclonal antibodies are disadvantageous because they fail to bind to some prostate tumors.